The main objective of the project is to search for unrecognized bladder carcinogens in the human environment. Drugs, food additives, and industrial compounds are being considered. The metabolism of suspect chemicals will be examined in urine to determine whether carcinogenic N-hydroxy metabolites are formed. Gas chromatography utilizing the electron capture detector, HPLC and GC-mass spectrometry will be the primary analytical methods used. Compounds being studied include caffeine, theobromine, theophylline, sulfadiazine, p-aminosalicylic acid, ampicillin, phenacetin, acetaminophen and acetanilid. Industrial amines being evaluated in dogs are methylenedianiline, 4,4'-methylene-bis(2-chloroaniline) dichlorobenzidine, 2,2-bis(p-amino-phenyl) propane and 4,4'-methylene-bis-('2-methylaniline). The N-hydroxy and nitroso derivatives of these amines are being synthesized. Previous results show that dimethylnitrosamine is formed in the bladder during urinary tract infection. If DMN is an etiological factor in bladder cancer, it must be shown that it can be activated by and react with bladder mucosa. Examination of bladder mucosa has shown the presence of cytochrome P-450 which is capable of type II binding. These microsomes are capable of N-hydroxylating 4-aminobiphenyl. Possible activation of DMN is still under investigation. Experiments to demonstrate the importance of the induction of hyperplasia by the naphthylamines and the inhibitions of this effect by retinoic acid will be carried out. The anticarcinogenic effect of 1-naphthylamine against 2-naphthylamine will be investigated.